Even though tangible progress toward biologically inspired tooth regeneration has been made and the ultimate goal appears more within reach than ever, significant efforts may still be required to accomplish therapeutic applicability of basic research findings toward dental regenerative medicine and to turn the dream of dental regeneration into practical reality. In order to respond to the emerging challenges and opportunities in tooth organ regeneration, we have recruited a Chicago- based research team together with national and international collaborators to generate a concept development plan for a U54 Specialized Center dedicated to the purpose of dental tissue regeneration. Together, our team is prepared to provide answers to the challenges of dental tissue regeneration. In order to address individual research questions, we have paired local experts with partners outside of Chicago, and leaders in dental tissue biology with cutting edge scientists in the fundamental subjects necessary for the success of the entire endeavor. For the planning phase, we have focused on four principal themes. Theme 1. To develop strategies for the implementation of entire tooth organ regeneration. Theme 2. To design methods and bio-inspired concepts to engineer tooth enamel. Theme 3. To conceive approaches toward dentin regeneration. Theme 4. To devise novel concepts toward periodontal regeneration. We propose that the realization of our plan will provide the blueprint for clinically successful dental tissue regeneration, generate further tools and insights toward medical organ regeneration, and yield in additional strategies for the prevention of oral disease and regeneration of oral tissues. [unreadable] [unreadable] [unreadable]